高脂肪食または肥満誘発性高脂肪食を与えられたマウスにおいて、食事性メチルグリオキサールは主に脂肪組織の機能不全を介して腎臓の脂肪毒性を誘発する

Unhealthy dietary patterns may impair renal function through elevated dietary methylglyoxal (MG) and advanced glycation end products (AGEs). While adipose tissue stores triglycerides (TG), its dysfunction promotes ectopic lipotoxicity, a process exacerbated by MG or AGEs. This study investigated if long-term dietary MG causes renal damage, mediated by adipose tissue dysfunction and ectopic lipid deposition. Eight-week-old male ICR mice were randomized into four groups for 52 weeks: normal diet and obesogenic high-fat diet (HFD), each with or without 1% MG in drinking water. HFD significantly increased MG-AGEs in both adipose tissue and kidneys. Although it caused adipocyte hypertrophy, the HFD-induced renal injury was observed despite the lack of kidney lipid accumulation. Concurrently, MG administration induced renal lipotoxicity and injury, manifested by increased TG concentrations in both the cortex and medulla. In HFD-fed mice, MG further exacerbated adipose tissue dysfunction by inhibiting angiogenesis and increasing interstitial collagen accumulation. Moreover, the MG co-administration reduced adipocyte size, a finding contrary to the hypertrophy caused by HFD alone. Furthermore, in the kidneys of these HFD-fed mice, MG led to increased medullary TG concentration and elevated collagen expression. In conclusion, HFD alone caused non-lipotoxic kidney injury without significant adipose dysfunction. However, MG administration consistently induced adipose tissue dysfunction and progressive renal lipotoxicity regardless of the diet. These findings suggest that MG-induced renal damage is primarily mediated by the dysfunction of adipose tissue, establishing a critical link between dietary MG intake and kidney disease progression, independent of obesogenic diet status.